The purpose of this contract is to understand the pathogenesis of important respiratory and enteric viral pathogens of humans and to develop means to prevent illness caused by these viruses. Johns Hopkins University will provide volunteers and a facility in which to study the biology of medically important viruses in humans, to examine the hosts' immune response to these viruses and to test new candidate live virus vaccines for safety, genetic stability, immunogenicity, transmissibility and protective efficacy Studies will also include administration of wild type viruses to volunteers in order to assess virulence. Subsequently, these wild viruses will be used to challenge vaccinated volunteers in order to assess the extent of immunity induced by candidate vaccines. Studies with vaccines will include an evaluation of their safety, immunogenicity, transmissibility, and protective safety. These studies will include both adult and pediatric subjects since the viruses studied cause disease in both these populations; e.g., influenza A viruses causes severe respiratory disease in the elderly and, conversely, respiratory syncytial virus causes severe respiratory disease in infants. In summary, this contract will provide both the facility and volunteers, (adult and pediatric populations) to study the biology and immunology of a variety of viral pathogens and will serve as a testing center for the development of new vaccines effective against these agents.